Recombinant Human Elastase Treatment of Cephalic Veins
- Corresponding Author:
- Steven K Burke
Proteon Therapeutics, Inc. 200 West Street Waltham, MA 02451,USA
E-mail: [email protected]
Received date: February 29, 2016; Accepted date: March 31, 2016; Published date: April 05, 2016
Citation: Wong MD, Bingham K, Moss E, Warn JD, Smirnov I, et al. (2016) Recombinant Human Elastase Treatment of Cephalic Veins. Cardiovasc Pharm Open Access 5:178. doi:10.4172/2329-6607.1000178
Copyright: © 2016 Wong MD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Vessel injury at the time of Arteriovenous Fistula (AVF) creation may lead to neointimal hyperplasia that impairs AVF maturation. Vonapanitase, a recombinant human chymotrypsin-like elastase family member 1, is an investigational drug under development to improve AVF maturation and patency. The current studies were designed to document vonapanitase effects in human cephalic veins that are used in AVF creation.
Methods: Human cephalic veins were mounted on a perfusion myograph. Vonapanitase 1.2, 4, 13.2, and 40 μg/ml or saline was applied drop wise on the vein followed by saline rinse. Vein segments were cut into rings for elastin content determination by desmosine radioimmunoassay and histology. Fluorescently-labelled vonapanitase was applied to veins and adventitial imaging was performed using laser scanning confocal microscopy. In vivo time course experiments were performed by treating rabbit jugular veins and harvesting 1 h and 4 h after vonapanitase treatment.
Results / Conclusion: Vonapanitase reduced desmosine content in a dose-related manner. Histology also confirmed a dose-related reduction in elastic fiber staining. Fluorescently-labelled vonapanitase persistently localized to elastic fibers in the vein adventitia. In vivo experiments showed a reduction in desmosine content in jugular veins from 1 h to 4 h following treatment. These data suggest that vonapanitase targets elastin in elastic fibers in a dose related manner and that elastase remains in the vessel wall and has catalytic activity for at least 1 h.